A Bayesian framework for pathway-guided identification of cancer subgroups by integrating multiple types of genomic data

Abstract

In recent years, comprehensive cancer genomics platforms, such as The Cancer Genome Atlas (TCGA), provide access to an enormous amount of high throughput genomic datasets for each patient, including gene expression, DNA copy number alterations, DNA methylation, and somatic mutation. While the integration of these multi-omics datasets has the potential to provide novel insights that can lead to personalized medicine, most existing approaches only focus on gene-level analysis and lack the ability to facilitate biological findings at the pathway-level. In this article, we propose Bayes-InGRiD (Bayesian Integrative Genomics Robust iDentification of cancer subgroups), a novel pathway-guided Bayesian sparse latent factor model for the simultaneous identification of cancer patient subgroups (clustering) and key molecular features (variable selection) within a unified framework, based on the joint analysis of continuous, binary, and count data. By utilizing pathway (gene set) information, Bayes-InGRiD does not only enhance the accuracy and robustness of cancer patient subgroup and key molecular feature identification, but also promotes biological understanding and interpretation. Finally, to facilitate an efficient posterior sampling, an alternative Gibbs sampler for logistic and negative binomial models is proposed using Pólya-Gamma mixtures of normal to represent latent variables for binary and count data, which yields a conditionally Gaussian representation of the posterior. The R package "INGRID" implementing the proposed approach is currently available in our research group GitHub webpage (https://dongjunchung.github.io/INGRID/).

Keywords: Bayesian model; biological pathway; clustering; integrative analysis; variable selection.